Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection

Viruses. 2017 Oct 5;9(10):289. doi: 10.3390/v9100289.


The progressive loss of immunological memory during aging correlates with a reduced proliferative capacity and shortened telomeres of T cells. Growing evidence suggests that this phenotype is recapitulated during chronic viral infection. The antigenic volume imposed by persistent and latent viruses exposes the immune system to unique challenges that lead to host T-cell exhaustion, characterized by impaired T-cell functions. These dysfunctional memory T cells lack telomerase, the protein capable of extending and stabilizing chromosome ends, imposing constraints on telomere dynamics. A deleterious consequence of this excessive telomere shortening is the premature induction of replicative senescence of viral-specific CD8+ memory T cells. While senescent cells are unable to expand, they can survive for extended periods of time and are more resistant to apoptotic signals. This review takes a closer look at T-cell exhaustion in chronic viruses known to cause human disease: Epstein-Barr virus (EBV), Hepatitis B/C/D virus (HBV/HCV/HDV), human herpesvirus 8 (HHV-8), human immunodeficiency virus (HIV), human T-cell leukemia virus type I (HTLV-I), human papillomavirus (HPV), herpes simplex virus-1/2(HSV-1/2), and Varicella-Zoster virus (VZV). Current literature linking T-cell exhaustion with critical telomere lengths and immune senescence are discussed. The concept that enduring antigen stimulation leads to T-cell exhaustion that favors telomere attrition and a cell fate marked by enhanced T-cell senescence appears to be a common endpoint to chronic viral infections.

Keywords: EBV; HBV; HCV; HDV; HHV-8; HIV; HPV; HSV; HTLV; VZV; exhaustion; senescence; telomerase; telomere.

Publication types

  • Review

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / physiology
  • Cell Differentiation
  • Cell Proliferation
  • Cellular Senescence*
  • Chronic Disease
  • Herpesvirus 1, Human / immunology
  • Herpesvirus 4, Human / immunology
  • Herpesvirus 8, Human / immunology
  • Humans
  • Immunologic Memory
  • Immunosenescence*
  • Mice
  • Telomere / immunology*
  • Telomere / pathology
  • Telomere Shortening
  • Virus Diseases / immunology*
  • Virus Diseases / metabolism